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Immune Reconstitution and Thymic Involution in the Acute and Delayed Hematopoietic Radiation Syndromes.
Health Physics ( IF 1.0 ) Pub Date : 2020-9-19 , DOI: 10.1097/hp.0000000000001352
Tong Wu 1 , P Artur Plett 1 , Hui Lin Chua 1 , Max Jacobsen 2 , George E Sandusky 2 , Thomas J MacVittie 3 , Christie M Orschell 1
Affiliation  

Lymphoid lineage recovery and involution after exposure to potentially lethal doses of ionizing radiation have not been well defined, especially the long-term effects in aged survivors and with regard to male/female differences. To examine these questions, male and female C57BL/6 mice were exposed to lethal radiation at 12 wk of age in a model of the Hematopoietic-Acute Radiation Syndrome, and bone marrow, thymus, spleen, and peripheral blood examined up to 24 mo of age for the lymphopoietic delayed effects of acute radiation exposure. Aged mice showed myeloid skewing and incomplete lymphocyte recovery in all lymphoid tissues. Spleen and peripheral blood both exhibited a monophasic recovery pattern, while thymus demonstrated a biphasic pattern. Naïve T cells in blood and spleen and all subsets of thymocytes were decreased in aged irradiated mice compared to age-matched non-irradiated controls. Of interest, irradiated males experienced significantly improved reconstitution of thymocyte subsets and peripheral blood elements compared to females. Bone marrow from aged irradiated survivors was significantly deficient in the primitive lymphoid-primed multipotent progenitors and common lymphoid progenitors, which were only 8-10% of levels in aged-matched non-irradiated controls. Taken together, these analyses define significant age- and sex-related deficiencies at all levels of lymphopoiesis throughout the lifespan of survivors of the Hematopoietic-Acute Radiation Syndrome and may provide a murine model suitable for assessing the efficacy of potential medical countermeasures and therapeutic strategies to alleviate the severe immune suppression that occurs after radiation exposure.

中文翻译:

急性和迟发性造血辐射综合征的免疫重建和胸腺退化。

暴露于潜在致死剂量的电离辐射后淋巴谱系恢复和退化尚未明确,尤其是对老年幸存者的长期影响以及男性/女性差异。为了研究这些问题,在造血-急性辐射综合征模型中,雄性和雌性 C57BL/6 小鼠在 12 周龄时暴露于致死辐射,并检查了长达 24 个月的骨髓、胸腺、脾脏和外周血。急性辐射暴露的淋巴细胞生成延迟效应的年龄。老年小鼠在所有淋巴组织中均表现出髓系偏斜和淋巴细胞恢复不完全。脾脏和外周血均表现出单相恢复模式,而胸腺则表现出双相模式。与年龄匹配的非辐照对照相比,老年辐照小鼠的血液和脾脏中的幼稚 T 细胞以及胸腺细胞的所有亚群均减少。有趣的是,与女性相比,受辐射的男性经历了胸腺细胞亚群和外周血成分的重建显着改善。来自老年辐射幸存者的骨髓显着缺乏原始淋巴激发的多能祖细胞和常见淋巴祖细胞,它们仅为年龄匹配的非辐射对照的 8-10%。综合起来,
更新日期:2020-12-17
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